Decreased bone tissue mineralization can partly explain subchondral sclerosis observed in osteoarthritis

Cox, Lge Lieke; Donkelaar, van René René; Rietbergen, van B Bert; Emans, P.J.; Ito, Keita

doi:10.1016/j.bone.2012.01.024

Cited by 58 publications

(67 citation statements)

References 41 publications

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“…Furthermore, in another study by Cox et al . (2012) noted that in OA the changes in subchondral bone mineralization occur only beneath the areas of significant cartilage destruction [33]. It can be, therefore, suggested that the subchondral sclerosis by itself is not the key factor in OA but rather the increased remodeling as it also causes structural and biochemical changes that affect the functionality of subchondral plate.…”

Section: Discussionmentioning

confidence: 99%

Subchondral bone histology and grading in osteoarthritis

et al. 2017

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ObjectiveOsteoarthritis (OA) has often regarded as a disease of articular cartilage only. New evidence has shifted the paradigm towards a system biology approach, where also the surrounding tissue, especially bone is studied more vigorously. However, the histological features of subchondral bone are only poorly characterized in current histological grading scales of OA. The aim of this study is to specifically characterize histological changes occurring in subchondral bone at different stages of OA and propose a simple grading system for them.Design20 patients undergoing total knee replacement surgery were randomly selected for the study and series of osteochondral samples were harvested from the tibial plateaus for histological analysis. Cartilage degeneration was assessed using the standardized OARSI grading system, while a novel four-stage grading system was developed to illustrate the changes in subchondral bone. Subchondral bone histology was further quantitatively analyzed by measuring the thickness of uncalcified and calcified cartilage as well as subchondral bone plate. Furthermore, internal structure of calcified cartilage-bone interface was characterized utilizing local binary patterns (LBP) based method.ResultsThe histological appearance of subchondral bone changed drastically in correlation with the OARSI grading of cartilage degeneration. As the cartilage layer thickness decreases the subchondral plate thickness and disorientation, as measured with LBP, increases. Calcified cartilage thickness was highest in samples with moderate OA.ConclusionThe proposed grading system for subchondral bone has significant relationship with the corresponding OARSI grading for cartilage. Our results suggest that subchondral bone remodeling is a fundamental factor already in early stages of cartilage degeneration.

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Section: Discussionmentioning

confidence: 99%

Subchondral bone histology and grading in osteoarthritis

et al. 2017

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“…Importantly, subchondral bone from OA patients is reported to be undermineralized (31) and may contribute to the subchondral bone sclerosis observed. As such, our finding that hypoxia reduces osteoblast mineralized bone nodule formation suggests that the hypomineralized OA bone could be driven by vascular remodeling and local hypoxia.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia Modulates the Phenotype of Osteoblasts Isolated From Knee Osteoarthritis Patients, Leading to Undermineralized Bone Nodule Formation

Chang

Jackson

Wardale

et al. 2014

Arthritis & Rheumatology

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ObjectiveTo investigate the role of hypoxia in the pathology of osteoarthritic (OA) bone by exploring its effect on the phenotype of isolated primary osteoblasts from patients with knee OA.MethodsOA bone samples were collected at the time of elective joint replacement surgery for knee or hip OA. Normal bone samples were collected postmortem from cadaver donors. Primary osteoblasts were isolated from knee OA bone chips and cultured under normoxic or hypoxic (2% O2) conditions. Alkaline phosphatase activity was quantified using an enzymatic assay, and osteopontin and prostaglandin E2 (PGE2) production was assayed by enzyme-linked immunosorbent assay. Total RNA was extracted from bone and osteoblasts, and gene expression was profiled by quantitative reverse transcription–polymerase chain reaction.ResultsHuman OA bone tissue sections stained positively for carbonic anhydrase IX, a biomarker of hypoxia, and exhibited differential expression of genes that mediate the vasculature and blood coagulation as compared to those found in normal bone. Culture of primary osteoblasts isolated from knee OA bone under hypoxic conditions profoundly affected the osteoblast phenotype, including the expression of genes that mediate bone matrix, bone remodeling, and bone vasculature. Hypoxia also increased the expression of cyclooxygenase 2 and the production of PGE2 by OA osteoblasts. Osteoblast expression of type II collagen α1 chain, angiopoietin-like 4, and insulin-like growth factor binding protein 1 was shown to be mediated by hypoxia-inducible factor 1α. Chronic hypoxia reduced osteoblast- mineralized bone nodule formation.ConclusionThese findings demonstrate that hypoxia can induce pathologic changes in osteoblast functionality consistent with an OA phenotype, providing evidence that hypoxia is a key driver of OA pathology.

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“…Accordingly, the average linear attenuation coefficient per pixel (measured by micro-CT) in SCL bone was higher than SHAM bone. Linear attenuation coefficient can be considered proportional to local degree of mineralization (Shahnazari et al, 2010;Cox et al, 2012). A higher linear attenuation coefficient per pixel could correspond to increased mineralization, contributing to changes in local creep response of SCL bone.…”

Section: Discussionmentioning

confidence: 99%